ObjectiveTo observe the effect of Liuwei Dihuangwan on behavioral impairments in the rat model of autism spectrum disorder （ASD） and explore the mechanism of action. MethodsTwelve SD pregnant rats were intraperitoneally injected with valproic acid （VPA） （10 rats） or normal saline （2 rats）， and male offspring were selected to establish the model of ASD and the control rats. Rats were randomly assigned into model， low-dose （0.75 g·kg^-1） and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan， vitamin D （positive drug， 3.7×10^-5 g·kg^-1）， and blank groups. Each group was administrated with the corresponding concentration of drugs or the same volume of normal saline by gavage for 2 weeks. After the intervention， the three-chamber social test was conducted to evaluate social interaction and social preference. The open field test was carried out to observe spontaneous behavior and anxiety state. Hematoxylin-eosin staining （HE） was used to observe the pathological changes of the prefrontal tissue. Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in prefrontal neurons. Immunofluorescence was used to detect the expression of ionized calcium-binding adapter molecule-1 （Iba-1） in the prefrontal tissue. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was employed to assess the expression differences of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated Unc-51-like autophagy-activating kinase 1 （p-ULK1）， Unc-51-like autophagy-activating kinase 1 （ULK1）， and FUN14 domain-containing protein 1 （FUNDC1）. ResultsCompared with the blank group， the model group spent less time sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.01） and showed reductions in the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.01）. In addition， the model group showed extensive apoptosis of neurons， with shrunken nuclei and red-stained cytoplasm， and extensive necrosis of neurons in the prefrontal tissue， mitochondrial swelling， decreased matrix density， disrupted cristae， and autophagic lysosomes in neurons， increases in the rate of Iba-1 positive cells in the prefrontal area （P<0.01） and the levels of TNF-α and IL-6 （P<0.01）， and down-regulation in the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. Compared with the model group， low-dose and high-dose Liuwei Dihuangwan and the vitamin D prolonged the time spent sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.05， P<0.01）， increased the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.05， P<0.01）， restored the morphology of neurons in the prefrontal tissue， decreased the number of apoptotic cells， alleviated the swelling of mitochondria in neurons， increased the matrix density， mitigated the fragmentation and disorder of cristae， and increased the number of autophagosomes. Moreover， the drugs decreased the rate of Iba-1 positive cells in the prefrontal area （P<0.01）， lowered the levels of TNF-α and IL-6 （P<0.01）， and up-regulated the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. ConclusionLiuwei Dihuangwan ameliorate autism-like behaviors and reduce neuronal apoptosis and neuroinflammatory damage in the rat model of ASD by promoting mitophagy mediated by the AMPK/ULK1/FUNDC1 pathway.

Objective:To investigate the association between albumin-corrected anion gap(ACAG)and short-to long-term death out-comes in patients with acute pancreatitis(AP).Methods:This retrospective study was based on the Medical Information Mart for Inten-sive Care-IV database,and the adult patients who were diagnosed with AP and were admitted to the intensive care unit were enrolled in this study.Cox regression risk analysis,receiver operating charac-teristic(ROC)curve analysis,Kaplan-Meier survival curve analy-sis,restricted cubic spline,and subgroup analysis were used to in-vestigate the value of ACAG in predicting the death outcome of AP patients.Results:A total of 444 patients were enrolled in this study,and according to the death status of the patients on day 28 after ad-mission,the patients were divided into survival group with 412 pa-tients and death group with 32 patients,with a mortality rate of 7.2%on day 28 after admission.The multivariate Cox regression analysis showed that ACAG was an independent predictive factor for all-cause mortality rate on day 28 after admission in AP patients(hazard ratio[HR]=1.18,95%CI=1.05-1.32),while it was not an in-dependent predictive factor for death outcome on days 90(HR=1.05,95%CI=0.97-1.14)and 180(HR=1.01,95%CI=0.94-1.09)and at 1 year(HR=1.02,95%CI=0.95-1.10).The ROC curve analysis showed that ACAG had an area under the ROC curve(AUC)of 0.732(95%CI=0.632-0.832)in predicting 28-day death outcome,which was better than that of AG(AUC=0.665,95%CI=0.550-0.781)and serum albumin(Alb)(AUC=0.655,95%CI=0.550-0.761)and was similar to that of Sequential Organ Failure Assessment(SOFA)score(AUC=0.745,95%CI=0.651-0.838).The ROC curve showed that the optimal cut-off value of ACAG was 21.375.Based on the cut-off value of ACAG of 21.375,the patients were divided into high-value group and normal-value group,and the Kaplan-Meier curve analysis showed that the patients with a high level of ACAG had a significantly higher mortality rate than those with normal ACAG(P<0.001).The subgroup analysis showed that the results were stable.Conclusion:ACAG can be used as an independent pre-dictive factor for all-cause mortality rate on day 28 after admission in AP patients,with a better efficacy than AG and Alb and a similar efficacy to SOFA.However,it is not significantly associated with 90-day,180-day,and 1-year death outcomes in AP patients.

Objective:To investigate the protective mechanism of cerium oxide nanoparticles(CeO2 NPs)against acute pancreatitis(AP),with a focus on their antioxidant and anti-inflammatory properties.Methods:CeO2 NPs were characterized by transmission elec-tron microscopy(TEM)and dynamic light scattering.In in vitro experiments,cell counting Kit-8(CCK-8)assay,flow cytometry,and Western blotting were used to validate the role of CeO2 NPs in preventing the apoptosis of pancreatic acinar cells.In in vivo experi-ments,C57BL/6 mice were divided into control group,AP group,AP+CeO2 group,SAP group,and SAP+CeO2 group to investigate the mechanism of action of CeO2 NPs in alleviating inflammation and oxidative stress in AP mice.Results:CeO2 NPs demonstrated rela-tively good stability and biocompatibility,with a particle size of(50±4)nm on TEM.In vitro experiments showed that CeO2 NPs sig-nificantly reduced the apoptosis of pancreatic acinar cells by alleviating lipid peroxidation and maintaining mitochondrial membrane potential.In vivo experiments showed that CeO2 NPs could reduce the serum levels of amylase,lipase,and inflammatory cytokines(in-terleukin-6 and tumor necrosis factor-α).This result might be related to the regulation of the IKK/P53/Bcl-2 pathway.CeO2 NPs re-duced the production of reactive oxygen species and enhanced anti-oxidant response by regulating the Nrf-2 signaling pathway.Con-clusion:CeO2 NPs exert anti-inflammatory and antioxidant effects by regulating the IκB kinase/tumor protein p53/B-cell lymphoma 2(IKK/P53/bcl-2)and nuclear factor erythroid 2-related(Nrf-2)signaling pathways,thereby showing promising potential for the treatment of AP.

Objective To explore the effect of 2-aminoethoxy-diphenyl borate(2-APB)on H2O2-induced chondro-cyte apoptosis and its mechanism.Methods The experiment was divided into control group,H2O2 group,2-APB group and H2O2+2-APB group.CCK-8 method was used to detect the cell viability of each group;The effect of 2-APB on the morphological changes of chondrocytes induced by H2O2 was observed under microscopy;TUNEL meth-od and flow cytometry were used to detect chondrocyte apoptosis;Flow cytometry was used to detect Lipid reactive oxygen species(ROS);Western blot was used to detect the protein expressions of Cleaved-PARP,p-PKCα and HIF-1α in H2O2-induced cells by 2-APB;Immunofluorescence was used to detect the fluorescent expression of HIF-1α in cells induced by H2O2 by PKCα inhibitor BIM-1.Results 2-APB inhibited H2O2-induced apoptosis in chon-drocytes,and the inhibitory effect was the most significant when the concentration of 2-APB was 100 pmol/L(F=235.80,P＜0.01);22-APB could inhibit the positive rate of H2O2-induced apoptosis of chondrocytes(F=114.80,P＜0.01)and the level of ROS(F=52.99,P＜0.01).and inhibited the expression of Cleaved-PARP(F=10.10,P＜0.05),p-PKCα(F=24.56,P＜0.05)and HIF-1α proteins(F=6.85,P＜0.05).The PKCα in-hibitor BIM-Ⅰ could inhibit the increase in HIF-1α fluorescence intensity caused by H2O2.Conclusion 2-APB can inhibit chondrocytes apoptosis induced by H2O2 through the PKCα/HIF-1α pathway and thus protect chondro-cytes.

Objective:To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL).Methods:Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed.Results:492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations ( P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive ( P<0.05). Conclusions:The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

【Objective】 To explore the feasibility of en-bloc resection of bladder tumors by flexible cystoscope combined with laparoscopic instruments through urethra and to provide reference for the clinical application of this technique. 【Methods】 Self-designed and processed transurethral single-hole PORT and Olympus electronic cystoscope were used as observation mirror; Φ1.8 mm soft grasper, tissue scissors, electric hook, and ultrasonic scalpel were used as instruments; the porcine bladder was used as a model.The PORT was placed through the urethra, and the cystoscope was inserted to observe the inner wall of the bladder and the condition of the mucosa.After the lesion site was identified in the bladder cavity, the soft grasper was inserted to pull the mucosa to be removed, which was then fixed with tension at the target position to maintain a satisfactory feild of view.The surgeon held the cystoscope in the left hand, and operated the laparoscopic instruments into the bladder cavity through the PORT with the right hand.Observing with the cystoscope and lifting and pulling the mucosa with the grasper, the surgeon simulated the cutting and pushing actions to realize the en-bloc resection of the lesioned mucosa. 【Results】 The mucosa at 4 different locations were successfully resected on 2 in vitro porcine bladder models. 【Conclusion】 The in vitro experiments show that the combination of flexible electronic cystoscope and laparoscopic instruments achieves synergistic effects in en-bloc resection of bladder tumor by transurethral single-hole laparoscope without additional iatrogenic bladder injury caused by percutaneous bladder incision.This method is feasible in the treatment of bladder tumors, and has the potential of clinical application after further optimization.

Tumor is one of the major diseases that endanger people’s health. At present, the treatments used for tumor include surgery, chemotherapy, radiotherapy and so on. Nonetheless, the traditional treatments have some disadvantages, such as insufficient treatment effect, liable to cause multidrug resistance, toxicity and side effect. Further research and exploration of tumor treatment schemes are still necessary. As the energy converter of cells, mitochondria are currently considered to be one of the most important targets for the design of new drugs for tumor, cardiovascular and neurological diseases. Nano-drug delivery carriers have the characteristics of being easily modified with active targeting groups, and it can achieve accurate targeted drug delivery to cells and organelles. This paper reviews the application of mitochondrial targeted nanoparticles in tumor diagnosis and treatment from the aspects of inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor recurrence and metastasis, and inducing cell autophagy.

Background and purpose:Breast cancer is a major global public health problem.Bone is the most common site of distant metastasis of breast cancer,accounting for about 70%of all metastatic cases.Bone metastasis of breast cancer can cause a series of complications,including severe pain,pathological fracture,hypercalcemia,spinal cord compression,etc.,which bring great inconvenience to patients'physical activities and affect their quality of life.Metastatic recurrence is the leading cause of death in breast cancer patients.Therefore,there is an urgent need to build a diagnostic model of bone metastasis in breast cancer to identify patients with a high risk of bone metastasis.The aim of this study was to develop a predictive model based on machine learning to predict the probability of breast cancer developing bone metastasis.Methods:Data of breast cancer patients diagnosed between 2010 and 2015 were extracted from The Surveillance,Epidemiology,and End Results(SEER)database.The variables were screened by least absolute shrinkage and selection operator(LASSO)regression,univariate and multivariate logistic regression analysis,and statistically significant risk factors were included to build a prediction model.In this study,nine machine learning algorithms,including decision tree,elastic network,K-nearest neighbor,lightweight gradient elevator,logistic regression,neural network,random forest,support vector machine and limit gradient lifting,were used to adjust the model hyperparameters through random search and 5x cross-validation to build a breast cancer bone metastasis prediction model.The area under the receiver operating characteristic(ROC)curve,calibration curve and decision curve were used to evaluate the model,the optimal model was obtained,and the importance of variables was analyzed based on the optimal model.Finally,a network calculator for predicting the risk of bone metastasis of breast cancer was established using the optimal model.Results:The study included 10 106 patients with breast cancer,7 073 patients in the training set,and 3 033 patients in the validation set.We found that 4 494(63.5%)patients in the training set and 1 927(63.5%)patients in the validation set developed bone metastases,respectively.Race,pathologic grade,estrogen receptor(ER)status,progesterone receptor(PR)status,human epidermal growth factor receptor 2(HER2)status,N stage,lung metastasis,radiotherapy,chemotherapy and surgery were independent predictors of bone metastasis.The training set and verification set were used to verify the model,and the limit gradient lifting algorithm was superior to other machine learning algorithms by integrating the evaluation indexes such as the area under the ROC curve,calibration curve and decision curve.Finally,we used limit gradient algorithm to build network calculator for prediction of breast cancer bone metastases(https://bcbm.shinyapps.io/DynNomapp/).Conclusion:This study developed a predictive model based on machine learning to predict the probability of bone metastases in breast cancer patients,hoping to help clinicians make more rational treatment decisions.

Objective To explore characteristics of co-infection of Chlamydia pneumoniae(Cpn)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and identify their effect on SARS-CoV-2-induced inflammatory response.Methods Patients with coronavirus disease 2019(COVID-19)who received treatment in a hospital in Chenzhou City from December 20,2022 to February 20,2023 were selected.According to the severity of COVID-19,severe and critical cases were classified as the severe symptom group,while mild and moderate cases were classified as the mild symptom group.Meanwhile,according to the age of patients(≥18 years old as adults,＜18 years old as juveniles),they were divided into the adult severe symptom group,adult mild symptom group,juvenile severe symptom group,and juvenile mild symptom group.Propensity score was adopted to match age,gender,and under-lying diseases of patients in severe symptom and mild symptom group in a 1∶1 ratio.Bronchoalveolar lavage fluid(BALF),throat swabs,and serum specimens of patients were collected.Cpn IgG/IgM antibody was detected by enzyme-linked immunosorbent assay(ELISA),levels of 12 common cytokines(including interleukin-8[IL-8])in BALF were detected by flow cytometry,differences among groups were compared.Results A total of 102 patients were included,with 61 severe and critical(severe symptom)patients,as well as 41 mild and moderate(mild symp-tom)patients.There were 71 patients aged ≥18 years and 31 juvenile patients aged＜18 years.There were 39 pa-tients in the adult severe symptom group and 32 in the adult mild symptom group,and 30 pairs were successfully matched through propensity score analysis.There were 22 patients in the juvenile severe symptom group and 9 in the juvenile mild symptom group,and 8 pairs were successfully matched through propensity score analysis.Among COVID-19 patients,the positive rates of Cpn IgG and IgM were 36.27％(n=37)and 8.82％(n=9),respective-ly,with 1 case positive for both Cpn IgG and IgM.The level of interferon(IFN)-α in serum specimens from adult patients with severe symptom combined with positive Cpn IgG was higher than that of IgG negative patients(P=0.037).There was no statistically significant difference in the levels of other cytokines in BALF and serum speci-mens between the two groups of patients(all P＞0.05).The levels of IL-8 and IL-17 in serum specimens of patients with positive Cpn IgG in the adult mild symptom group were both higher than those in Cpn IgG negative patients(both P＜0.05).The levels of IL-8 in both BALF and serum specimens from Cpn IgM positivity patients in the ju-venile mild symptom group were higher than those from patients with negative Cpn IgM(both P＜0.05).Logistic regression analysis results showed that Cpn IgG and IgM positivity were not risk factors for the development of se-vere COVID-19.Conclusion Combined Cpn infection is not a risk factor for the development of severe symptom in COVID-19 patients,and Cpn infection has limited impact on the secretion of inflammatory factors caused by SARS-CoV-2.

Objective To study the effect of performance evaluation based on analytic hierarchy process combined with paperless electronic medical record management system applied in medical record management on the quality of medical records.Methods According to the standard of filling out medical record information in our hospital,100 cases of medical records were selected randomly for quality assessment from January 2023 to January 2024.Medical record management before and after the im-plementation of performance random based on analytic hierarchy process combined with paperless electronic medical record man-agement system was observed,including the quality of medical records,defects in medical records,the time for organizing medi-cal records of the discharged patients,satisfaction of all kinds of personnel and management of medical records.Results The score for quality of medical records after implementation was higher than that before implementation(P＜0.05).The incidence rates of defects in medical records such as insufficient differential diagnosis,delayed recording of special examinations,incom-plete examination forms,omissions in informed consent forms,omissions in special project approval forms,incomplete medication indications,excessive medication for discharged patients,inconsistent medical orders and fee lists,and no registration within 72 hours were reduced(P＜0.05).The accuracy of coding,accuracy of archiving,recovery rate,and qualification rate of homepage were improved(P＜0.05).The time for organizing nursing documents and other medical records was shortened(P＜0.05).Satisfaction of nurses,physicians,staff responsible for transportation,and patients was improved(P＜0.05).Conclu-sion Applying performance evaluation based on analytic hierarchy process combined with paperless electronic medical record management system in medical record management can effectively improve the quality of medical records,reduce defects in medi-cal records,improve the efficiency of medical record management,shorten the time for organizing medical records of discharged patients,and enhance satisfaction of all kinds of personnel,reference can be considered.